Browsing by Author "Mangen, Fred Wabwire"

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    Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treating Uncomplicated Malaria: A Randomized Trial to Guide Policy in Uganda
    (PloS one, 2008) Yeka, Adoke; Dorsey, Grant; Kamya, Moses R.; Talisuna, Ambrose; Lugemwa, Myers; Rwakimari, John Bosco; Staedke, Sarah G.; Rosenthal, Philip J.; Mangen, Fred Wabwire; Bukirwa, Hasifa
    Uganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.Patients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0–28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI −0.2–7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.DP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.
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    Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial
    (PLoS clinical trials, 2007) Kamya, Moses R.; Yeka, Adoke; Bukirwa, Hasifa; Lugemwa, Myers; Rwakimari, John B.; Staedke, Sarah G.; Talisuna, Ambrose O.; Mangen, Fred Wabwire
    To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.Randomized single-blinded clinical trial.Apac, Uganda, an area of very high malaria transmission intensity.Children aged 6 mo to 10 y with uncomplicated falciparum malaria.Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%–26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%–19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%–12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%–16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.
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    Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria in Uganda
    (PLoS clinical trials, 2006) Bukirwa, Hasifa; Yeka, Adoke; Kamya, Moses R.; Talisuna, Ambrose; Banek, Kristin; Bakyaita, Nathan; Rwakimari, John Bosco; Rosenthal, Philip J.; Mangen, Fred Wabwire; Dorsey, Grant; Staedke, Sarah G.
    To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda.Randomized single-blind controlled trial.Tororo, Uganda, an area of high-level malaria transmission.Children aged one to ten years with confirmed uncomplicated P. falciparum malaria.Amodiaquine + artesunate or artemether–lumefantrine.Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether–lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether–lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%–24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether–lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%–25.2%). Amodiaquine + artesunate and artemether–lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens.Amodiaquine + artesunate and artemether–lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether–lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.
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    Clinical characteristics, treatment and outcome of childhood Burkitt’s lymphoma at the Uganda Cancer Institute
    (Transactions of the Royal Society of Tropical Medicine and Hygiene, 2011) Orem, Jackson; Mulumba, Yusuf; Algeri, Sara; Bellocco, Rino; Mangen, Fred Wabwire; Mbidde, Edward Katongole; Weiderpass, Elisabete
    Burkitt's lymphoma (BL) is a major cause of death among Ugandan children. We studied clinical characteristics and outcomes of childhood BL over time at the Uganda Cancer Institute (UCI). A total of 1217 children (766 boys, 451 girls, mean age 6.69 years) diagnosed with BL between 1985 and 2005 were included. There were no significant changes in the proportion of boys and girls diagnosed, or in mean age at diagnosis. Facial tumor (n = 945, 77.65%) and abdominal disease (n = 842, 69.19%) were the most common presentations. The proportion of children presenting with hepatic mass, malignant pleocytosis, and advanced-stage (stage C and D) BL increased during the study period (P < 0.01). A total of 1085 children out of 1206 (89.97%) received at least one cycle of chemotherapy, and 832 of 1099 (75.71%) demonstrated objective response (i.e. complete or partial remission). The most common symptoms at BL diagnosis were fever (n = 621, 51.03%), anemia (n = 593, 48.73%), and weight loss (n = 588, 48.32%). Significant increases in the proportion of children with fever, and significant changes in the proportion of children with anemia, night sweats and severe infection were observed. HIV positivity was 3.87%, but no substantial differences in the proportion of HIV-positive children were observed. Mortality was not significantly different over time: it was similar in boys and girls, higher in older children (compared with younger ones), in those with advanced-stage BL, and HIV-positive children, but lower in children with facial tumors compared with other tumor presentations, and among those who received chemotherapy.
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    Evaluation of the Safety and Efficiency of the Dorsal Slit and Sleeve Methods of Male Circumcision Provided by Physicians and Clinical Officers in Rakai, Uganda
    (BJU international, 2012) Buwembo, Dennis; Musoke, Richard; Kigozi, Godfrey; Sempijja, Victor; Serwadda, David; Makumbi, Frederick; Watya, Stephen; Namuguzi, Dan; Nalugoda, Fred; Kiwanuka, Noah; Sewankambo, Nelson K.; Mangen, Fred Wabwire; Lutalo, Tom; Kiggundu, Valerian; Anyokorit, Margaret; Nkale, James; Kighoma, Nehemia; Wawer, Maria J.; Gray, Ronald H.
    To assess safety and efficiency of the dorsal slit and sleeve male circumcision (MC) procedures performed by physicians and clinical officers.We evaluated the time required for surgery and moderate / severe adverse events (AEs), among circumcisions by trained physicians and clinical officers using sleeve and dorsal slit methods. Univariate and multivariate regression with robust variance was used to assess factors associated with time for surgery (linear regression) and adverse events (logistic regression). Six physicians and 8 clinical officers conducted 1934 and 3218 MCs, respectively. There were 2471 dorsal slit and 2681 sleeve procedures. The mean duration of surgery was 33 minutes for newly trained providers and decreased to ~20 minutes after ~100 circumcisions. The adjusted mean duration of surgery for dorsal slit was significantly shorter than that for sleeve method (Δ −2.8 minutes, p- <0.001). The duration of surgery was longer for clinical officers than physicians performing the sleeve procedure, but not the dorsal slit procedure. Crude AEs rates were 0.6% for dorsal slit and 1.4% with the sleeve method (p=0.006). However, there were no significant differences after multivariate adjustment. Use of cautery significantly reduced time needed for surgery (Δ − 4.0 minutes, p =0.008), but was associated with higher rates of AEs (adjusted odds ratio 2.13, 95%CI 1.26–3.61, p=0.005).The dorsal slit resection method of male circumcision is faster and safer than sleeve resection, and can be safely performed by non-physicians. However, use of cautery may be inadvisable in this setting.
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    HIV Modes of Transmission and Prevention Response Analysis
    (Uganda National AIDS Commission, 2009) Mangen, Fred Wabwire; Odiit, Martin; Kirungi, Wilford; Kisitu, David Kaweesa; Wanyama, James Okara
    This study is the outcome of close collaborative by a team in Uganda, with technical and financial support from the UNAIDS Regional Support Team for Eastern and Southern Africa, and UNAIDS Geneva. The UNAIDS Modes of Transmission model was customized for Uganda, and applied, to better understand pattern of new infections. The model results, together with existing epidemiological data and the conclusions of recently completed studies on the factors driving Uganda’s HIV epidemic, are compared with data on HIV funding allocations, to derive recommendations for strengthening Uganda’s HIV prevention response. This was part of a set of studies also done in Kenya, Lesotho, Mozambique, Swaziland and Zambia. The other countries focused more on synthesizing existing data and collecting new data to better know each country's HIV epidemic, comparing the epidemic with the national HIV response and funding allocation, also with the aim of improving HIV prevention based on evidence on what works to prevent new infections.
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    Impairments, Functional Limitations, and Access to Services And Education for Children with Cerebral Palsy in Uganda: A Population-Based Study
    (Developmental Medicine & Child Neurology, 2020) Andrews, Carin; Mwesige, Angelina Kakooza; Almeida, Rita; Peterson, Stefan Swartling; Mangen, Fred Wabwire; Eliasson, Ann-Christin; Forssberg, Hans
    To describe the functional limitations and associated impairments of children with cerebral palsy (CP) in rural Uganda, and care-seeking behaviour and access to assistive devices and education.Ninety-seven children with CP (42 females, 55 males; age range 2–17y) were identified in a three-stage population-based screening with subsequent medical examinations and functional assessments. Information on school and access to care was collected using questionnaires. The data were compared with Swedish and Australian cohorts of children with CP. We used the χ2 test and linear regression models to analyse differences between groups.Younger children were more severely impaired than older children. Two-fifths of the children had severe impairments in communication, about half had intellectual disability, and one third had seizures. Of 37 non-walking children, three had wheelchairs and none had walkers. No children had assistive devices for hearing, seeing, or communication. Care-seeking was low relating to lack of knowledge, insufficient finances, and ‘lost hope'. One-third of the children attended school. Ugandan children exhibited lower developmental trajectories of mobility and self-care than a Swedish cohort.The needs for children with CP in rural Uganda are not met, illustrated by low care-seeking, low access to assistive devices, and low school attendance. A lack of rehabilitation and stimulation probably contribute to the poor development of mobility and self-care skills. There is a need to develop and enhance locally available and affordable interventions for children with CP in Uganda.
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    Prevalence of Cerebral Palsy in Uganda: A Population-Based Study
    (The Lancet Global Health, 2017) Mwesige, Angelina Kakooza; Andrews, Carin; Peterson, Stefan; Mangen, Fred Wabwire; Eliasson, Ann Christin; Forssberg, Hans
    Few population-based studies of cerebral palsy have been done in low-income and middle-income countries. We aimed to examine cerebral palsy prevalence and subtypes, functional impairments, and presumed time of injury in children in Uganda.In this population-based study, we used a nested, three-stage, cross-sectional method (Iganga-Mayuge Health and Demographic Surveillance System [HDSS]) to screen for cerebral palsy in children aged 2–17 years in a rural eastern Uganda district. A specialist team confirmed the diagnosis and determined the subtype, motor function (according to the Gross Motor Function Classification System [GMFCS]), and possible time of brain injury for each child. Triangulation and interviews with key village informants were used to identify additional cases of suspected cerebral palsy. We estimated crude and adjusted cerebral palsy prevalence. We did χ2 analyses to examine differences between the group screened at stage 1 and the entire population and regression analyses to investigate associations between the number of cases and age, GMFCS level, subtype, and time of injury.We used data from the March 1, 2015, to June 30, 2015, surveillance round of the Iganga-Mayuge HDSS. 31 756 children were screened for cerebral palsy, which was confirmed in 86 (19%) of 442 children who screened positive in the first screening stage. The crude cerebral palsy prevalence was 2·7 (95% CI 2·2–3·3) per 1000 children, and prevalence increased to 2·9 (2·4–3·6) per 1000 children after adjustment for attrition. The prevalence was lower in older (8–17 years) than in younger (<8 years) children. Triangulation added 11 children to the cohort. Spastic unilateral cerebral palsy was the most common subtype (45 [46%] of 97 children) followed by bilateral cerebral palsy (39 [40%] of 97 children). 14 (27%) of 51 children aged 2–7 years had severe cerebral palsy (GMFCS levels 4–5) compared with only five (12%) of 42 children aged 8–17 years. Few children (two [2%] of 97) diagnosed with cerebral palsy were born preterm. Post-neonatal events were the probable cause of cerebral palsy in 24 (25%) of 97 children.Cerebral palsy prevalence was higher in rural Uganda than in high-income countries (HICs), where prevalence is about 1·8–2·3 cases per 1000 children. Children younger than 8 years were more likely to have severe cerebral palsy than older children. Fewer older children than younger children with cerebral palsy suggested a high mortality in severely affected children. The small number of preterm-born children probably resulted from low preterm survival. About five times more children with post-neonatal cerebral palsy in Uganda than in HICs suggested that cerebral malaria and seizures were prevalent risk factors in this population.